Antimicrobial composition and method of use

ABSTRACT

A BIOCIDAL COMBINATION OF 2,4,5-TRICHLOROPHENOL AND METHYLENE BISTHIOCYANATE USEFUL FOR THE PROTECTION OF LEATHER AND FOR OTHER FIELDS WHERE BIOCIDAL TREATMENT IS DESIRED.

ANTIMICROBIAL COMPOSITION AND METHOD OF USE Louis I. Feldman, Spring Valley, N.Y., assignor to .Baxrer Laboratories, Inc., Morton Grove, III., a corporation of Delaware No Drawing. Filed Mar. 14, 1967, Ser. No. 622,939

' Int. Cl. A01n 9/18 us. or. 424-402 9 Claims ABSTRACT OF THE DISCLOSURE This invention relates to antimicrobial compositions and more particularly to synergistic antifungal compositions containing 2,4,5-trichlorophenol and methylene bisthiocyanate: I

The control of microorganisms is a persisting problem. The variety. of organisms and the varying conditions under which control is needed present particular problems-which do not admit of easy solutions. Protection againstrnicroorganisms such as bacteria and fungi is necessary in many fields such as the textile, paper, leather, wood, coatings and food industries. Many types of preservatives have beenfemployed in these and other such fields for protection against attack by microorganisms.

In the leather industry where the hides and skins of animals are processed into a variety of products, the animal origin of the leather product provides a famrable nutrient medium for the growth of microorganisms such as fungi and bacteria. At several stages in the preparation of leatherjfrom animal skins and hides, microbial'f attack is an important problem, and the use of biocides is required to prevent damage to the hides or leather. Hides, after remoyal from the animal carcass, are preserved prior to leather-making by salting, which is a process that dehydratesgthe-hides. Properly salted hides are not readily .attacked by microorgani ms. However, prior to le'jathermaking, the hides must be rehydrated by soaking, making them again susceptible to the growth of microorganisms. During the soaking period, biocides generally are added to inhibit microbial growth.

Following the liming (dehairing), bating, pickling and tanning steps in leather manufacture, the tanned hides generally are stored for variable periods of time under a \ariety of conditions. Tanned hides under storage bonditions can be attacked by microorganisms, especially fungi. Thus, it is good practice to protect these tanned hides by application of an antifungal agent. Finished leather exposed to high humidity also is susceptible to fungal growth, whereby it is generally considered desirable to have a fungicide present on the finished leather.

Among the various compounds suggested, for biocidal purposes, the halophenols have been Widely-used aspreservatives and are known to have desirable antimicrobial properties. The halophenols also are frequently used in admixture with other compounds and materials in order to provide improved results. An example of such combinations is disclosed in US. Pat. 1,879,351, where halophenols, for example trichlorophenol, are used in conjunction with benzoic acid and substituted benzoic acids or derivatives thereof.

Various organic mercury or zinc compounds and orga'nosulfur compounds also are known to have effective antimicrobial properties. Included in the latter group of compounds are the organic thiocyanates and in particu- .rr wliii aa 5;

3 @555 s 15* e" r I 11 3,555,159 Patented Jan. 12, 1971 lar, for purposes of the present invention, methylene bis- 3,555,159 thiocyanate. The antimicrobial properties of methylene bisthiocyanate are disclosed in US. Pat. 3,252,855.

In selecting an appropriate biocide, properties such as toxicity, odor, color, and stability as well as specificity for particular organisms or broad range antimicrobial activity should be-taken into consideration. For example, in the leather industry in conjunction with the use of the halophenols, it is common practice to extend the range of activity against microorganisms by combining a compound having primarily antibacterial activity (such as pentachlorophenol with a second compound having primarily antifungalactivity (such as trichlorophenol). It is known, however, that the antimicrobial agents presently in general use in the leather industry suffer from a variety of deficiencies, which include insufficient efiectiveness, instability, toxicity, and incapacity to restrain resistance development.

In brief, the present invention, as distinguished from prior combinations for extending the antimicrobial range of activity, is concerned with the use of two compounds having substantially different chemical moieties, namely 2,4,5-trichlorophenol and methylene bisthiocyanate, in a synergistic antifungal combination. It has been found according to thegpresent invention that said compounds can be combined in admixture with each other to provide a substantial and significant mutual enhancement of antifungal activity.

A principal advantage of the present combination is that lower concentrations of each component are required to achieve the same antifungal effectiveness as a larger concentration of the individual components alone. Use of lower concentrations reduces toxicity as well as the cost of application. Another advantage in the practice of the present invention, particularly since the combination employs two substantially different chemical moieties, is

that the improved antifungal activity will be complemented with a broader antimicrobial spectrum of activity and with hinderance to resistance development.

The 2,4,5-trichlorophenol component of the present invention can be ,ieadily prepared by treatment of 1,2, 4,5-tetrachloroben.iene with methanolic NaOH in an autoclave at l60fifjC. for several hours. The methylene bisthiocyanate component can be prepared by first reacting methylene chloride with sodium iodide and hydrochloric acid in acetone solvent and thereafter reacting the. resulting product with sodium thiocyanate under conventional refluxing temperatures and conditions. Although these specific methods of preparation of the active antifungal components of the present invention are disclosed, it will be understood that the invention is not limited to any particular method of preparation of these components.

In carrying out the present invention, the ratio of the active components to each other can vary somewhat but it is preferred to combine about one part by weight of methylene bisthiocyanate with from about 5 to about 20 parts by weight of 2,4,5-trichlorophenol.

In practice, the antifungal combination of 2,4,5-trichlorophenol and methylene bisthiocyanate can be used in admixture with various diluents, solid and liquid carriers,

surface active agents, and also with other antimicrobially effective additives.

In the case of solid carriers, materials having large surface areas such as bentonite, kieselguhr, fullers earth, clay, pyrophylite talc and the like can be employed as well as nonclay carriers such as lignocellulose and wood When it is desired to use the antifungal combination of the present invention in liquid form, it is desirable to dissolve or disperse the combination in a liquid carrier.

sEARcH oomy? Water, alcohols, and various oils and organic solvents can be used. Suitable oils include those of animal, vegetable, mineral and synthetic origin such as soy bean oil, castor oil, cod liver oil, kerosene and the like.

Dispersion of the active antifungal components in a liquid carrier can be promoted by agitation in the presence of a surface active agent. Any of the well-known emulsifying or dispersing agents may be employed for this purpose, for example, sodium louryl sulfate, aliphatic and aromatic sulfonates such as sulfonated castor oil or various alkaryl sulfonates such as the sodium salt of monosulfonated nonyl napthalene. Non-ionic types of emulsifying agents can also be used such as the higher molecular weight alkyl polyglycol ethers. The amount of surface active agent in the liquid formulation will generally range from about 1% to about 20% by weight of the active antifnngal components.

The range of concentration of the total active antifungal components in the liquid or solid formulations used in practice can vary somewhat and will depend, in part, on the particular end use to which the formulation is put. Concentrations as low as a fraction of 1% by weight of the active components may be used, for example, concentrations as low as about 0.1%. Very highly concentrated formulations, for example, those containing EXAMPLE 1 A liquid formulation of the antifungal combination of the present invention containing 20% 2,4,5-trichlorophenol and 2% methylene bisthiocyanate by weight is prepared as follows:

(A) To 2 grams of methylene bisthiocyanate (Cytox 3040) add 62 grams of cresylic acid and stir until solution is achieved. Add grams of methanol and grams of 2,4,5-trichlorophenol (Dowicide 2). Stir the blend until in solution and then add one gram of sodium-N- methyl-N-oleoyltaur-ate (Igepon T-33).

An alternative method of preparing the above formulation is to blend together the cresylic acid, alcohol and surface active agent and then add the active antimicrobial materials.

The above liquid formulation is an excellent antimicrobial composition which exhibits activity against a broad spectrum of fungi and bacteria. This formulation is useful for preservation in the leather, textile, paper, coatings, and other industries. In the above formulation, the ratio of the active materials to each other can vary from about one part of methylene bisthiocyanate to from about five parts to about twenty parts by weight of the 2,4,5-trichlorophenol with substantially equivalent anti microbial results.

In the above example, other diluent materials, for ex- :ample, kerosene, mineral spirits, linseed oil and naphthol can be substituted for the diluent cresylic acid with sub- :stantially equivalent results. Other alcohols, for example t'isopropanol, butanol and ethanol can besubstituted for the methanol with substantially equivalent results and other emulsifying agents, for example, sodium-N-cyclo- Ihexyl-N-palmitoyltaurate and the oleic acid ester of sodium isethionate can be substituted for the sodium-N- methyl-N-oleoyltaurate with substantially equivalent results.

EXAMPLE 2 tions (B and C) which were identical to A in every respect except that 13 did not contain the methylene bisthiocyanate and C did not contain the 2,4,5-trichlorophenol. These formulations were tested at several dilutions for antifungal activity on petri dishes inoculated with a mixture of Aspergillus oryzae and A. niger, and incubated at 30 C. for 7 days. The results were as follows:

Concentration required for growth inhibition (meg/g.)

Formulation:

A 5.88 'lCP plus 0.59 MBT.

TOP.

N OTE.TCP=2,4,5-trichloruphenol; MBT=methylene bisthiocyanate The effectiveness of the combination of 2,4,5-trichorophenol and methylene bisthiocyanate as a leather preservative is demonstrated by the following test made on leather stock in the blue received immediately out of the tan drum.

Procedure (1) Leather strips cut /2" x 6" (about 30 g./strip) were either (a) soaked in the test solution (equal weights of test solution and leather strips placed 'on reciprocating shaker for 30 minutes), or (b) dipped in the test solution (equal weights of test solution and leather strips in petri dish in which the leather strips were pulled slowly through, the test solution).

(2) Tanners Fungal Spore Culture on sand was sprinkled on both sides (grain and flesh) of the leather test strips.

(3) The inoculated leather test strips were incubated at 30 C. for up to 18 days in barrel jars containing water in the bottom of the jar.

Results Growth (days) Soak Di Concentration, 6 8 percent Formulation Sterozol N N OTE. =no growth; =growth.

The above test results show that the formulation A containing the combination of 2,4.5-trichlorophenol and methylene bisthiocyanate inhibits fungi at a significantly lower concentration than does the Sterozol N formulation used for purposes of comparison and that the formulation A combination is about two times better than an equivalent amount of Sterozol N.

Various modifications and adaptations of the hereindefined invention can be made, after reading the foregoing specification and claims appended hereto, by the person skilled in the art without'departingjf-rom the spirit and scope of {the invention. All such modifications and adaptations are incluuded within the scopeof the invention as defined in the appended claims.

What is claimed is:

1. An 'antifungal composition comprising from about to about 20 parts by weight of 2,4,5 trichlorophenol and about one part by weight of methylene bisthiocyanate.

2; The antifungal composition of claim 1 wherein the 2,4,5-trichloropheno1 is present in an amount of about parts by weight of the methylene bisthiocyanate.

3. The method of inhibiting the growth of fungi comprising applying to a substance which is subject to attack by fungia fungus inhibiting amount of the composition of claim 1.

4. The method of inhibiting the growth of fungi comprising applying to a substance which .is subject to attack by fungia fungus inhibiting amount of the composition of claim "2.

5. An'antifun gal composition comprising from about 0.1% to about 50% by weight of a inixture of the composition of claim 1 and from about 99.1% to about 50% by weight of antifungally inactive components selected from the group consisting of bentonite, kieselguhr, fullers earth, clay, pyrophilite talc, lignoceil-lulose, wood flour, water, methanol, ethanol, isopropanol, butanol, soybean oil, castor oil, cod liver oil, linseed oil, kerosene, cresylic acid, mineral spirits, naphthol, sodium lauryl sulfate, sulfonated castor oil, sodium salt of monosulfonated nonyl naphthalene, sodium-N-methyl-N-oleoyl-taurate, sodium- N-cyclohexyl-N-palmitoyltaurate and oleic acid ester of sodium isethionate.

6. The method of inhibiting the growth of fungi comprising applying to a substance which is subject to attack by fungi a fungus inhibiting amount of the composition of claim 5.

7. The method of inhibiting the growth of fungi on animal hides and leather comprising applying to the animal hide or leather a fungi inhibiting amount of the composition of claim 1.

8. The method of inhibiting the growth of fungi on animal hides and leather comprising applying to the animal hide or leather a fungi inhibiting amount of the composition of claim 2.

9. The method of inhibiting the growth of fungi on animal hides and leather comprisinng applying to the animal hide or leathera fungi inhibiting amount of the composition of claim 5.

References Cited UNITED STATES PATENTS 2,322,633 6/ 1943 Hitchens 16738.7 2,392,987 1/ 1946, Hill l67-38.7 2,849,360 8/1958 Polak 167-38.5 3,252,855 5/ 1966 Wehner 167-22 ALBERT T. MEY ERS, Primary Examiner D. R. ORE, Assistant Examiner US. Cl. X.R.

Notice of Adverse Decisions in Interferences In Interference No. 97,948 involvin Patent No. 3,555,159, L. I. Feldman, ANTIMICROBIAL COMPOSITION ND METHOD OF USE, final judgment adverse to the patentee was rendered Aug. 20, 1973, as to claims 1, 2, 3

and 4.

[Ofiicial Gazette N o'vember 2?, 1.973.] 

